The prevalence of arthritis has been increased gradually with an aging society, and the treatment and management of arthritis directly affect the quality of life of patients. In fact, the domestic prevalence of osteoarthritis over the age of 50 in 2010-2013 was overall 12.5% (5.1% for males and 18.9% for females), and the prevalence of osteoarthritis appears to increase with age. According to the current status of management of osteoarthritis, only 64.6% of the total osteoarthritis cases were diagnosed, and only about half of them were cured, showing that the disease becomes chronic with age (national health statistics, 2013; Korea Centers for Disease Control and Prevention of the Ministry of Health and Welfare). Therefore, the social demand for the development of novel drugs for treating arthritis and alleviating symptoms seems to continuously increase.
Polymeric hyaluronic acid or a pharmaceutically acceptable salt thereof has been used as a therapeutic agent for degenerative arthritis, rheumatoid arthritis, or the like. The hyaluronic acid or the pharmaceutically acceptable salt thereof is conventionally formulated into liquid injections to be directly administered to an affected area such as the joint of a knee, a shoulder, or the like, and it has been reported that the hyaluronic acid or the pharmaceutically acceptable salt thereof, which is a viscoelastic polymer substance, is also directly injected into the articular cavity to reduce the impact caused by the loss of cartilage tissue in a patient with arthritis during joint movement and to help a lubrication action, by which dysfunction caused by arthritis is improved and joint pain is suppressed as well as alleviating joint pain and normalizing a function of joint.
Meanwhile, a poorly soluble drug has problems of low solubility, poor releasability in the body, and the like, and thus efforts to improve the solubility and release behavior of a poorly soluble drug have been continuously made. A nonsteroidal anti-inflammatory drug (NSAID), which is one of poorly soluble drugs, generally refers to all types of drugs that are not steroids in terms of structure and are used for pyrexia, pain, inflammation, and the like, and has currently been used to treat degenerative arthritis due to its excellent analgesic and antiphlogistic actions and long half-life in blood. Particularly, piroxicam, which is one of the NSAIDs, has been proven to have excellent local anti-inflammatory and analgesic actions and also reported to effectively remove inflammation when directly administered to the articular cavity of arthroscopic surgery patients.
In addition, it was confirmed that when hyaluronic acid is administered in combination with some NSAIDs to the articular cavity, the effect of hyaluronic acid injections can be improved.
However, when a hyaluronic acid/NSAID is administered as an injection, there is a problem in which a pharmacological activity is decreased due to a decrease in molecular size and viscosity caused by the reduction-oxidation and a series of hydrolysis of hyaluronic acid, and piroxicam is precipitated (Korean Unexamined Patent Publication No. 1994-0001891).
Therefore, there is a need of novel formulation of a hyaluronic acid/NSAID having excellent stability and capable of maintaining a pharmacological activity for a long period.